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A Module Analysis Approach to Investigate Molecular Mechanism of TCM Formula: A Trial on Shu-feng-jie-du Formula.

Song J, Zhang F, Tang S, Liu X, Gao Y, Lu P, Wang Y, Yang H - Evid Based Complement Alternat Med (2013)

Bottom Line: We here proposed a computational approach integrating the module detection technique into a 2-class heterogeneous network (2-HN) which models the complex pharmacological system of a TCM formula.This approach takes three steps: construction of a 2-HN, identification of primary pharmacological units, and pathway analysis.Therefore, this approach is capable of uncovering the mode of action underlying a TCM formula via module analysis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.

ABSTRACT
At the molecular level, it is acknowledged that a TCM formula is often a complex system, which challenges researchers to fully understand its underlying pharmacological action. However, module detection technique developed from complex network provides new insight into systematic investigation of the mode of action of a TCM formula from the molecule perspective. We here proposed a computational approach integrating the module detection technique into a 2-class heterogeneous network (2-HN) which models the complex pharmacological system of a TCM formula. This approach takes three steps: construction of a 2-HN, identification of primary pharmacological units, and pathway analysis. We employed this approach to study Shu-feng-jie-du (SHU) formula, which aimed at discovering its molecular mechanism in defending against influenza infection. Actually, four primary pharmacological units were identified from the 2-HN for SHU formula and further analysis revealed numbers of biological pathways modulated by the four pharmacological units. 24 out of 40 enriched pathways that were ranked in top 10 corresponding to each of the four pharmacological units were found to be involved in the process of influenza infection. Therefore, this approach is capable of uncovering the mode of action underlying a TCM formula via module analysis.

No MeSH data available.


Related in: MedlinePlus

An illustration of SHU formula intervening the influenza development through multiple pathways. The blue rectangle is bioactive herbal compounds derived from SHU formula. The ellipse represents biological pathways that the compounds modulate. The red ones are literature-verified pathways that participate in the process of influenza infection, while the gray ones are not verified yet. A thick edge indicates many common hits (pathway components that are also associated targets of herbal compounds) between two pathways or between a compound and a pathway.
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fig3: An illustration of SHU formula intervening the influenza development through multiple pathways. The blue rectangle is bioactive herbal compounds derived from SHU formula. The ellipse represents biological pathways that the compounds modulate. The red ones are literature-verified pathways that participate in the process of influenza infection, while the gray ones are not verified yet. A thick edge indicates many common hits (pathway components that are also associated targets of herbal compounds) between two pathways or between a compound and a pathway.

Mentions: According to the results of pathway analysis, we built a simple network to illustrate the pharmacological action of SHU formula against influenza infection (Figure 3). This network was constructed based on module 1 identified by Girvan-Newman algorithm from the 2-HN of SHU formula. The edge connecting a compound and a pathway indicates the cooccurrence of associated targets of the compound and pathway components, while the edge between two pathways represents the commonness of hits (pathway components that are also associated targets of herbal compounds) corresponding to both pathways. As shown in Figure 3, 8 bioactive compounds of module 1 modulate 10 enriched pathways related to influenza infection. From the perspective of topology, resveratrol is the most important to regulate the involved pathways compared to other compounds. It is obvious that resveratrol is connected to all 10 pathways through strong links, indicating that resveratrol mediates multiple gene products in these pathways. Besides, resveratrol is found to modulate the G1/S-phase transition (P value 4.1e − 24) [47], the EGFR/HER2 signaling pathway (P value 2.8e − 20) [46], and the PTEN/AKT pathway (P value 5.3e − 16) [46]. Other compounds like Acteoside also perform similar functions on the involved pathways [77]. Of the top 10 enriched pathways, 7 (red ellipse) are found to participate in the development of influenza and its induced symptoms, illustrated in Table 5. Thus, the herbal compounds in Figure 3 are likely to intervene in the invasion, production, proliferation, and transition of influenza virus, through mediating multiple relevant pathways. Three pathways (grey ellipse) regulated by the compounds in Figure 3 hold great promise to influence the influenza development, while such prediction needs further work to test and verify.


A Module Analysis Approach to Investigate Molecular Mechanism of TCM Formula: A Trial on Shu-feng-jie-du Formula.

Song J, Zhang F, Tang S, Liu X, Gao Y, Lu P, Wang Y, Yang H - Evid Based Complement Alternat Med (2013)

An illustration of SHU formula intervening the influenza development through multiple pathways. The blue rectangle is bioactive herbal compounds derived from SHU formula. The ellipse represents biological pathways that the compounds modulate. The red ones are literature-verified pathways that participate in the process of influenza infection, while the gray ones are not verified yet. A thick edge indicates many common hits (pathway components that are also associated targets of herbal compounds) between two pathways or between a compound and a pathway.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3860149&req=5

fig3: An illustration of SHU formula intervening the influenza development through multiple pathways. The blue rectangle is bioactive herbal compounds derived from SHU formula. The ellipse represents biological pathways that the compounds modulate. The red ones are literature-verified pathways that participate in the process of influenza infection, while the gray ones are not verified yet. A thick edge indicates many common hits (pathway components that are also associated targets of herbal compounds) between two pathways or between a compound and a pathway.
Mentions: According to the results of pathway analysis, we built a simple network to illustrate the pharmacological action of SHU formula against influenza infection (Figure 3). This network was constructed based on module 1 identified by Girvan-Newman algorithm from the 2-HN of SHU formula. The edge connecting a compound and a pathway indicates the cooccurrence of associated targets of the compound and pathway components, while the edge between two pathways represents the commonness of hits (pathway components that are also associated targets of herbal compounds) corresponding to both pathways. As shown in Figure 3, 8 bioactive compounds of module 1 modulate 10 enriched pathways related to influenza infection. From the perspective of topology, resveratrol is the most important to regulate the involved pathways compared to other compounds. It is obvious that resveratrol is connected to all 10 pathways through strong links, indicating that resveratrol mediates multiple gene products in these pathways. Besides, resveratrol is found to modulate the G1/S-phase transition (P value 4.1e − 24) [47], the EGFR/HER2 signaling pathway (P value 2.8e − 20) [46], and the PTEN/AKT pathway (P value 5.3e − 16) [46]. Other compounds like Acteoside also perform similar functions on the involved pathways [77]. Of the top 10 enriched pathways, 7 (red ellipse) are found to participate in the development of influenza and its induced symptoms, illustrated in Table 5. Thus, the herbal compounds in Figure 3 are likely to intervene in the invasion, production, proliferation, and transition of influenza virus, through mediating multiple relevant pathways. Three pathways (grey ellipse) regulated by the compounds in Figure 3 hold great promise to influence the influenza development, while such prediction needs further work to test and verify.

Bottom Line: We here proposed a computational approach integrating the module detection technique into a 2-class heterogeneous network (2-HN) which models the complex pharmacological system of a TCM formula.This approach takes three steps: construction of a 2-HN, identification of primary pharmacological units, and pathway analysis.Therefore, this approach is capable of uncovering the mode of action underlying a TCM formula via module analysis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.

ABSTRACT
At the molecular level, it is acknowledged that a TCM formula is often a complex system, which challenges researchers to fully understand its underlying pharmacological action. However, module detection technique developed from complex network provides new insight into systematic investigation of the mode of action of a TCM formula from the molecule perspective. We here proposed a computational approach integrating the module detection technique into a 2-class heterogeneous network (2-HN) which models the complex pharmacological system of a TCM formula. This approach takes three steps: construction of a 2-HN, identification of primary pharmacological units, and pathway analysis. We employed this approach to study Shu-feng-jie-du (SHU) formula, which aimed at discovering its molecular mechanism in defending against influenza infection. Actually, four primary pharmacological units were identified from the 2-HN for SHU formula and further analysis revealed numbers of biological pathways modulated by the four pharmacological units. 24 out of 40 enriched pathways that were ranked in top 10 corresponding to each of the four pharmacological units were found to be involved in the process of influenza infection. Therefore, this approach is capable of uncovering the mode of action underlying a TCM formula via module analysis.

No MeSH data available.


Related in: MedlinePlus